Antigen processing of Mycobacterium bovis BCG vaccine substrains differs in mouse dendritic cells 2259586

Abstract

Abstract Introduction The BCG vaccine given at birth varies in its protective efficacy against tuberculosis that kills millions of people. We hypothesized that this could be due to a heterogeneity among BCG sub strains. Therefore, we examined their ex vivo immunogenicity using dendritic cells. Methods The DC.2.4 cell line derived from C57BL/6 mice were infected with Pasteur, Copenhagen, Japan, Moreau, and Russian strains, followed by an assay for their ability to present Antigen85B-derived peptide to CD4 T cells triggering IL-2; RNAseq analysis for gene expression; and proteomics. Results 1) Antigen presentation by Copenhagen infected DCs to T cells was better than others. 2) RNAseq data analyzed using KEGG, GO and Reactome analyses indicated that Copenhagen infected DCs showed a better enrichment of genes Involved in antigen processing, autophagy and cytokine-chemokine modules compared to others. 3) Proteomics confirmed that the antigen processing machinery (Cathepsins, MHC and autophagy-mediating proteins) was differentially upregulated; Copenhagen showed the greatest enrichment followed by Russian, Moreau, Pasteur and Japan. Conclusion We propose that BCG sub strains differ in DC-dependent T cell activation, likely to affect protection against tuberculosis. Funding Source NIH NIAID R01-AI-I87440 Topic Categories Vaccines and Immunotherapy (VAC)